A Phase 1b/2 clinical trial testing rebastinib, in combination with the chemotherapy medication carboplatin, in adults with breast cancer and patients with other advanced or metastatic solid tumors has begun, Deciphera Pharmaceuticals announced.
Recruitment for this open-label, multicenter study is ongoing at NEXT Oncology in San Antonio, but has yet to start at the MD Anderson Cancer Center in Houston. More information can be found here.
The study will be conducted in two parts. Part 1 will assess the safety, tolerability, and pharmacokinetics — a compound’s absorption, distribution, metabolism, and excretion in the body — of twice-daily doses of rebastibinib — 50 mg and 100 mg — in combination with carboplatin, delivered intravenously (into the vein). Rebastinib will be given orally, either in 25 or 75 mg tablets, in 21-day cycles.
This first part will help determine the optimal dose of rebastinib for further testing.
In part 2, the safety, tolerability, and efficacy of the recommended dose will be assessed across different groups, including breast cancer, ovarian cancer, and mesothelioma patients. The trial is expected to include up to 117 participants — approximately 18 in the first part, and up to 99 in the second part.
“We are extremely pleased with the recent progress made on our rebastinib program,” Michael D. Taylor, PhD, Deciphera’s president and CEO, said in a press release.
Based on preclinical results, the combination of rebastinib with carboplatin “has the potential to be an important new approach to treating patients with advanced solid tumors,” according to Taylor.
Rebastinib is an investigational small molecule that selectively inhibits the TIE2 kinase enzyme. TIE2 is the receptor for angiopoietins, a group of molecules that participate in blood vessel growth within tumors and activate pro-tumoral immune cells called macrophages.
Daniel L. Flynn, PhD, Deciphera’s chief scientific officer, said that the TIE2 kinase also regulates the factors that lead to tumor cell recruitment and metastasis.
In a previous Phase 1 trial, treatment with rebastinib increased the amount of the TIE2 ligand angiopoietin 2, which follows TIE2 inhibition.
Chemotherapy is believed to increase the recruitment of the pro-tumoral macrophages, boosting blood vessel density and dissemination in tumors, Flynn said, adding that “in preclinical studies, rebastinib has been shown to block these unintended effects of chemotherapy, providing rationale for the potential combination of rebastinib with chemotherapy.”
Besides this study, Rebastinib is being evaluated in another Phase 1b/2 trial (NCT03601897) in combination with Taxol (paclitaxel), and in a Phase 1b trial (NCT02824575) in people with metastatic breast cancer, given with Taxol or Eisai’s Halaven (eribulin mesylate).